| The oral anticoagulant warfarin is clinically administered as a racemic mixture of two enantiomers, (R) and (S). Many relevant drug interactions with warfarin have been attributed to the specific metabolic inhibition of the more pharmacologically active (S)-enantiomer.;In order to investigate reports that acetaminophen can potentiate the anticoagulant effect of warfarin, each of twenty healthy male volunteers were given single oral 20 mg doses of racemic warfarin on three occasions: (1) alone, (2) after one day of acetaminophen (4g/d) and (3) after two weeks of acetaminophen (4g/d).;The urinary excretion pattern of acetaminophen and its metabolites was not significantly altered over its course of administration.;The (R)- and (S)-enantiomers of warfarin exhibited significantly different pharmacokinetic properties. However, acetaminophen did not alter the disposition of either (R)- or (S)-warfarin.;All subjects exhibited a pharmacodynamic response to racemic warfarin. The response was not significantly altered in the presence of acute or chronic acetaminophen dosing as assessed by prothrombin time and factor VII concentrations. |
